The normal eucaryotic cell cycle typically comprises four main stages: the G.sub.1, S, G.sub.2, and M phases. The replication of DNA and the production of histones occur during the S phase. This period of DNA synthesis is flanked by two "gap" periods, the G.sub.1 and G.sub.2 phases, during which pre- and post-replication DNA repair may occur, respectively, and during which the cell continues to produce the cellular macromolecules required for cell division. After the G.sub.2 phase, the cell will enter the M phase, wherein the cell will divide by mitosis.
After irradiation, normal mammalian cells generally enter a period either where DNA synthesis is arrested, or where the cell is arrested in the G.sub.2 phase. This period of arrest provides a "checkpoint" in the cell cycle which allows time for the repair of damaged/mismatched DNA templates, and prevents the segregation of damaged chromosomes. Irradiation induced inhibition of DNA synthesis has been the subject of intensive research for many years (Hartwell and Weinert, 1989, Science). Recent results have reported a direct link between the ability of human cells to arrest in G.sub.1 phase following irradiation, and the status of the p53 tumor suppressor gene (Kasten et al., 1991 Cancer Res. 51:6304-6311; Kuerbitz et al., 1992, Pro. Natl. Acad. Sci. USA 89:7491-7495). In brief, these studies linked irradiation with increased levels of p53 protein. Further studies have demonstrated that inhibitors of protein kinase C (PKC) may prevent enhanced p53 expression after irradiation (Khanna & Lavin, 1993 Oncogene 8:3307-3312). These data cumulatively suggest that both PKC and p53 may play a role in irradiation induced inhibition of DNA synthesis.